ArticleThe Journal of clinical investigation2003
Increased islet apoptosis in Pdx1+/- mice.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.
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Who cites it
172 citing papers in PubMed, 309 citations in OpenAlex.
- MODY PDX1Frontiers in endocrinology · 2025Article
- Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs.Scientific reports · 2024Article
- Unveiling islet heterogeneity using an automated microfluidic imaging system.Scientific reports · 2024Article
- Tanycytic transcytosis inhibition disrupts energy balance, glucose homeostasis and cognitive function in male mice.Molecular metabolism · 2024Article
- β-cell neogenesis: A rising star to rescue diabetes mellitus.Journal of advanced research · 2024Review
- Angiotensin (1-7) Improves Pancreatic Islet Function via Upregulating PDX-1 and GCK: A Dose-Dependent Study in Mice.International journal of endocrinology · 2024Article
- IMT504 protects beta cells against apoptosis and maintains beta cell identity, without modifying proliferation.Physiological reports · 2023Article
- Deficiency of WTAP in islet beta cells results in beta cell failure and diabetes in mice.Diabetologia · 2023Article
- CaBiomedicines · 2023Review
- p53 Inhibition in Pancreatic Progenitors Enhances the Differentiation of Human Pluripotent Stem Cells into Pancreatic β-Cells.Stem cell reviews and reports · 2023Article
- The hippo kinases MST1/2 in cardiovascular and metabolic diseases: A promising therapeutic target option for pharmacotherapy.Acta pharmaceutica Sinica. B · 2023Review
- Effective Generation of Functional Pancreatic β Cells from Human-Derived Dental Stem Cells of Apical Papilla and Bone-Marrow-Derived Stem Cells: A Comparative Study.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Mesenchymal Stem Cells Secretions Enhanced ATP Generation on Isolated Islets during Transplantation.Islets · 2022Article
- Genetic Ablation of the Nutrient Sensor Ogt in Endocrine Progenitors Is Dispensable for β-Cell Development but Essential for Maintenance of β-Cell Mass.Biomedicines · 2022Article
- PDX-1: A Promising Therapeutic Target to Reverse Diabetes.Biomolecules · 2022Review
- Weight Cycling Impairs Pancreatic Insulin Secretion but Does Not Perturb Whole-Body Insulin Action in Mice With Diet-Induced Obesity.Diabetes · 2022Article
- Toward Precision Medicine with Human Pluripotent Stem Cells for Diabetes.Stem cells translational medicine · 2022Review
- Rare catastrophes and evolutionary legacies: human germline gene variants in MLKL and the necroptosis signalling pathway.Biochemical Society transactions · 2022Review
- PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetes.Cell death discovery · 2022Article
- HDL and Diabetes.Advances in experimental medicine and biology · 2022Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Mice with 50% Pdx1, a homeobox gene critical for pancreatic development, had worsening glucose tolerance with age and reduced insulin release in response to glucose, KCl, and arginine from the perfused pancreas. Surprisingly, insulin secretion in perifusion or static incubation experiments in response to glucose and other secretagogues was similar in islets isolated from Pdx1(+/-) mice compared with Pdx1(+/+) littermate controls. Glucose sensing and islet Ca(2+) responses were also normal. Depolarization-evoked exocytosis and Ca(2+) currents in single Pdx1(+/-) cells were not different from controls, arguing against a ubiquitous beta cell stimulus-secretion coupling defect. However, isolated Pdx1(+/-) islets and dispersed beta cells were significantly more susceptible to apoptosis at basal glucose concentrations than Pdx1(+/+) islets. Bcl(XL) and Bcl-2 expression were reduced in Pdx1(+/-) islets. In vivo, increased apoptosis was associated with abnormal islet architecture, positive TUNEL, active caspase-3, and lymphocyte infiltration. Although similar in young mice, both beta cell mass and islet number failed to increase with age and were approximately 50% less than controls by one year. These results suggest that an increase in apoptosis, with abnormal regulation of islet number and beta cell mass, represents a key mechanism whereby partial PDX1 deficiency leads to an organ-level defect in insulin secretion and diabetes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.